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Researchers Find Potential Path to a Broadly Protective COVID-19 Vaccine Using T cells

In This Article

  • In order to study HIV, Gaurav Gaiha, MD, DPhil, and Elizabeth Rossin, MD, PhD, previously developed an approach known as structure-based network analysis to identify viral pieces that are constrained, or restricted, from mutation
  • When the pandemic began, the researchers applied the principles of structure-based network to SARS-CoV-2
  • Their research revealed that it may be possible to develop a broadly protective T cell vaccine that can protect against variants of concern, such as the Delta variant, and potentially extend protection to future variants

In previous studies on mutations in human immunodeficiency virus (HIV), Gaurav Gaiha, MD, DPhil, researcher at the Ragon Institute of Mass General, MIT and Harvard, and Elizabeth Rossin, MD, PhD, a former retina fellow and incoming retina faculty member at Mass Eye and Ear, developed an approach to virus identification known as structure-based network analysis. The approach allows clinicians to identify viral pieces, or epitopes, that are constrained or restricted from mutation.

Dr. Gaiha and his team have now applied the principles of structure-based network analysis to SARS-CoV-2. By using the approach, the researchers identified mutationally constrained SARS-CoV-2 epitopes that can be recognized by immune cells known as T cells. These epitopes could then be used in a vaccine to train T cells to provide protective immunity. In Cell, they highlight the possibility of a T cell vaccine that could offer broad protection against new and emerging variants of SARS-CoV-2 and other SARS-like coronaviruses.

Previous studies indicated that patients with a robust T cell response, specifically a CD8+ T cell response, were more likely to survive COVID-19 infection. Dr. Gaiha's team combined their approach with these insights and identified 311 highly networked epitopes in SARS-CoV-2 likely to be both mutationally constrained and recognized by CD8+ T cells. After studying the presence and significance of all 311 epitopes, the team identified 53 epitopes that represented potential targets for a T cell vaccine and confirmed in a retroactive analysis that the epitopes identified could induce an immune reaction.

"A T cell vaccine that effectively targets these highly networked epitopes, would potentially be able to provide long-lasting protection against multiple variants of SARS-CoV-2, including future variants," said Dr. Rossin, who is co–first author of the study with Anusha Nathan, a medical student in the Harvard-MIT Health Sciences and Technology program.

In order to test their predictions on new variants of SARS-CoV-2, the team obtained sequences from the B.1.1.7 Alpha, B.1.351 Beta, P1 Gamma and B.1.617.2 Delta SARS-CoV-2 variants. They compared these sequences with the original SARS-CoV-2 genome, cross-checking the genetic changes against their highly networked epitopes. Remarkably, of all the mutations they identified, only three mutations were found to affect highly networked epitopes sequences, and none of the changes affected the ability of these epitopes to interact with the immune system.

While the current mRNA vaccines provide strong protection against COVID-19, Dr. Gaiha says, it's unclear if they will continue to provide equally strong protection as more and more variants of concern begin to circulate.

This study shows that it may be possible to develop a broadly protective T cell vaccine that can protect against the variants of concern, such as the Delta variant, and potentially extend protection to future variants and similar coronaviruses that may emerge.

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Learn more about the Ragon Institute of MGH, MIT and Harvard

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